Pain can be modulated by explicit beliefs about treatments, prior experience and learning, interpersonal processes that support the patient-provider relationship, and contextual factors related to the treatment environment. In this project, we systematically investigate the neural and psychological mechanisms that mediate the effects of these factors on acute pain. We focus on expectations, attention, emotion, conditioning/associative learning, and social factors. Our experiments principally use functional magnetic resonance imaging (fMRI) and psychophysiological measurements, as well as behavioral assays and self-reports. We are examining the effects of different types of pain-related expectations on decisions about pain as well as responses in the brain and body. We also plan to compare acute pain with other hedonic and perceptual processes. This will allow us to distinguish processes that are unique to pain perception from those that are not specific to pain, such as processes involved in perception and decision-making across domains. This was our first year, and we focused on setting up the lab (the Section on Affective Neuroscience and Pain) and beginning data collection. The human subjects protocol Neural and psychological mechanisms of pain perception received approval from the NINDS Protocol Implementation Review Committee and the Institutional Review Board. The protocol includes five sub-studies designed to a) isolate different aspects of pain modulation, b) compare acute pain modalities (e.g., thermal pain versus shock-induced pain), and c) compare and contrast pain with other hedonic and perceptual domains (e.g., taste). In all studies, we measure decisions about pain experience (self-report) as well as neural and physiological responses to noxious stimuli that cause pain. During analysis, we will combine computational modeling with advanced neuroimaging analyses to isolate the neural and psychological mechanisms that mediate the effects of expectations, attention, and emotion on subjective pain. During the protocol approval process, we hired lab personnel, established laboratory standards, and developed our experiment room in the Outpatient Center. We can now administer noxious thermal stimuli (calibrated to each individuals pain sensitivity) while simultaneously collecting physiological responses, including pupil diameter, skin conductance, heart rate (via electrocardiogram and peripheral pulse) and respiration. Our computer tasks are self-paced based on patient eye movements, which allows us to use gaze position as an additional dependent measure in our tasks. Data collection commenced in May of this year. We have completed testing on 23 healthy volunteers who participated as behavioral pilots in our first sub-study. Following screening, all participants completed questionnaires, followed by a pain calibration procedure that measures pain ratings in response to noxious heat stimuli and determines each participants pain threshold and tolerance. Participants then went on to a pilot sub-study designed to examine the effects of classical conditioning and instructed knowledge on pain and reversal learning. Data from our behavioral sub-studies are used for task development prior to fMRI scanning, as well as for effect size estimation and power analysis. Three summer students analyzed data from these initial pilot subjects. Preliminary analyses of our data from the pain calibration indicate that a) our healthy volunteers show statistical relationships between noxious stimulus temperature and reported pain; 2) pupil diameter is correlated with noxious heat and subjective pain reports; 3) skin conductance response amplitude correlates with noxious heat and subjective pain. Preliminary analyses of our behavioral pilot data indicate possible dissociations between cue-based expectancy effects on pain reports and skin conductance responses. We aim to collect four more pilot participants in our current variant of the first sub-study, and then will estimate our effect size and perform power analyses to determine sample size for the fMRI sub-study. We anticipate the first fMRI sub-study will begin in several weeks, at the end of FY15 or the start of FY16.